Chronic pain syndrome is a heterogeneous group of diseases characterized by several pathological mechanisms. One in five adults in Europe may experience chronic pain. In addition to the individual burden, chronic pain has a significant societal impact because of work and school absences, loss of work, early retirement, and high social and healthcare costs. Several anti-inflammatory treatments are available for patients with inflammatory or autoimmune diseases to control their symptoms, including pain. However, patients with degenerative chronic pain conditions, some with 10-fold or more elevated incidence relative to these manageable diseases, have few long-term pharmacological treatment options, limited mainly to non-steroidal anti-inflammatory drugs or opioids. For this review, we performed multiple PubMed searches using keywords such as "pain," "neurogenic inflammation," "NGF," "substance P," "nociception," "BDNF," "inflammation," "CGRP," "osteoarthritis," and "migraine." Many treatments, most with limited scientific evidence of efficacy, are available for the management of chronic pain through a trial-and-error approach. Although basic science and pre-clinical pain research have elucidated many biomolecular mechanisms of pain and identified promising novel targets, little of this work has translated into better clinical management of these conditions. This state-of-the-art review summarizes concepts of chronic pain syndromes and describes potential novel treatment strategies.